Antiviral therapy 2016 12 07() doi 10.3851/IMP3116
In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), maraviroc-containing treatment regimens were not associated with increased hepatotoxicity.
In this randomised, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (clinicaltrials.gov identifier, NCT01327547). The primary endpoint was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary endpoints included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography, and an optional biopsy substudy.
Through 144 weeks of treatment, 2 (maraviroc) and 3 (placebo) patients met the protocol-defined Grade 3/4 ALT endpoint. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on MVC) showed signs of decreased fibrosis. One (maraviroc) and 2 (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs vs 3 in the placebo group. One death in the maraviroc group and 2 deaths in the placebo group were reported.
Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.